The focus of this research is the application of recombinant DNA techniques to the study of familial melanoma. Previous studies have demonstrated weak genetic linkage between the Rh locus on the short arm of chromosome 1 and an autosomal dominant gene responsible for familial cutaneous malignant melanoma (CMM) and its associated precursor lesion, the dysplastic nevus syndrome (DNS). We will use recombinant DNA techniques to increase the number of genetic markers on chromosome 1. We will isolate and characterize DNA sequences from chromosome 1 and use these sequences as DNA hybridization probes to detect restriction fragment length polymorphisms (RFLPs) segregating in families carrying the CMM/DNS gene. The analysis of the inheritance of these DNA markers in relation to the CMM/DNS gene will permit a definitive test of the localization of this gene to chromosome 1. If the gene is located on chromosome 1, the use of recombinant DNA techniques will allow its location to be established with a high degree of precision. The precise localization of the gene will permit a number of significant diagnostic questions to be addressed.It will be possible to determine whether all families exhibiting familial melanoma are segregating a gene at the same chromosomal location; it should permit diagnostic evaluation of family members within such families via genetic linkage techniques. The localization of the gene to a specific chromosomal segment will permit the initiation of studies to identify the specific gene responsible for this syndrome. (6)